Z-drug abuse and dependence: clinical guideline of the Brazilian Academy of Neurology for diagnosis and management

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Abstract
Benzodiazepine (BZD) receptor agonists, commonly known as Z-drugs, are non-BZD hypnotics primarily prescribed for the treatment of insomnia. Their use is recommended for no longer than four weeks to minimize the risk of adverse effects, including dependence and withdrawal. However, these guidelines are frequently disregarded, and the abuse of and dependence on Z-drugs has emerged as a growing public health concern in Brazil. The present article reviews the current evidence on Z-drug use disorder—including dependence and withdrawal—and proposes clinical guidelines for the management of discontinuation. The recommendations were developed based on a systematic review of the literature and refined using the Delphi methodology. The consensus was developed by a multidisciplinary task force, with coordination and voting led by a steering committee. An advisory committee, consisting of neurologists from the Brazilian Academy of Neurology (Academia Brasileira de Neurologia, ABN, in Portuguese) and psychiatrists specializing in substance-use disorders, contributed to the selection and organization of the scientific literature and took part in the voting process. Key recommendations were established: 1) prior to discontinuation, a comprehensive assessment of mental status, psychiatric and sleep comorbidities, and the degree of pharmacological dependence is essential; 2) gradual tapering is advised; 3) non-pharmacological interventions, such as cognitive behavioral therapy for insomnia, are recommended, and acceptance and commitment therapy, which is optional, may be incorporated; 4) for zolpidem withdrawal, adjunctive pharmacotherapy, which is optional, may include trazodone, other antidepressants, quetiapine or other antipsychotics, alpha-2-delta (α2δ) ligands, or alternative hypnotics (such as ramelteon, zopiclone, and eszopiclone); 5) for Z-drug discontinuation, intermediate- or long-acting BZDs are recommended; and 6) short- or ultra-short-acting BZDs and immediate-release melatonin are not recommended.

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